The present invention relates to apparatus and methods for performing percutaneous myocardial revascularization and injecting autologous materials into the treated tissue to stimulate angiogenesis.
A leading cause of death in the United States today is coronary artery disease, in which atherosclerotic plaque causes blockages in the coronary arteries, resulting in ischemia of the heart (i.e., inadequate blood flow to the myocardium). The disease manifests itself as chest pain or angina. In 1996, approximately 7 million people suffered from angina in the United States.
One technique that has been developed to treat patients suffering from diffuse atherosclerosis, is referred to as percutaneous myocardial revascularization (PMR). In this method, a series of channels are formed in the left ventricular wall of the heart extending inward from the myocardium. Typically, between 15 and 30 channels about 1 mm in diameter and preferably several millimeters deep are formed with a laser in the wall of the left ventricle to perfuse the heart muscle with blood coming directly from the inside of the left ventricle, rather than traveling through the coronary arteries. Commonly assigned U.S. Pat. No. 5,910,150 to Saadat describes mechanical apparatus for forming such channels. PCT Publication WO 98/17186 describes a laser-based system for performing PMR that includes needle adjacent to the laser element for injecting a contrast agent to mark the position of the PMR channels for imaging.
U.S. Pat. No. 5,840,059 to Mar. et al. describes a laser-based PMR system that deposits a angiogenic agent, such as a gene vector or genetically engineered harvested cells, into the channel formed during the PMR procedure to promote angiogenesis. A drawback of this approach, however, is that blood pulsing through the PMR channel during normal cardiac wall motion may cause the angiogenic factor to be promptly washed out of the channel, thereby dissipating any beneficial effect obtainable from its introduction.
In addition, it is relatively difficult and expensive to use engineer and produce the kinds of angiogenic factors referred to in the foregoing patent.
Accordingly, it would be desirable to provide apparatus and methods for delivering angiogenic agents in conjunction with PMR treatments that promote long-term residence of the angiogenic agent in the vicinity of the treated tissue. It further would be desirable to provide relatively low-cost and readily available or readily prepared angiogenic agents for use in conjunction with PMR.
Wartiovaara et al., xe2x80x9cPeripheral Blood Platelets Express VEGF-C and VEGF which Are Released During Platelet Activation,xe2x80x9d Thromb Haemost, 80:171-175 (1998), describes that a variety of vascular endothelial growth factors (VEGF) may be derived from platelets. Knighton et al., xe2x80x9cRole of Platelets and Fibrin in the Healing Sequence,xe2x80x9dAnn. Surg., 196(4)379-388 (1982), which is incorporated herein by reference, describes that thrombin-activated platelets, when injected in vivo in rabbit corneas, produced neovascularization that was dose related. U.S. Pat. Nos. 4,957,742 to Knighton, U.S. Pat. No. 4,479,896 to Antoniades, and U.S. Pat. No. 5,834,418 to Brazeau describe methods of extracting platelet growth factors from blood.
Sakai et al., xe2x80x9cAutologous Cardiomyocyte Transplantation Improves Cardiac Function After Myocardial Injury,xe2x80x9d presented at the 1999 STS Convention, San Antonio, N. Mex., Jan. 1999, suggests that autologous cardiomyocytes may be harvested, cultured and re-injected into injured myocardium to restore ventricular function.
In view of the foregoing, it would be desirable to provide apparatus and methods for using autologous materials in conjunction with PMR to augment angiogenesis resulting from forming myocardial channels.
It further would be desirable to provide apparatus and methods that reduce the risk of such autologous angiogenic materials from washing out of the PMR channels, and instead promote retention of such materials by injecting the angiogenic materials into the myocardium adjacent to the PMR channels.
In view of the foregoing, it is an object of this invention to provide apparatus and methods for delivering angiogenic agents in conjunction with PMR treatments that promote long-term residence of the angiogenic agent in the vicinity of the treated tissue.
It is another object of the present invention to provide apparatus and methods for conveniently and economically preparing autologous angiogenic agents for use in conjunction with PMR.
It is another object of this invention to provide apparatus and methods for using autologous materials in conjunction with PMR to augment angiogenesis resulting from forming myocardial channels.
It is also an object of the present invention to provide apparatus and methods that reduce the risk of such autologous angiogenic materials from washing out of the PMR channels, and instead promote retention of such materials.
It is a further object of the present invention to provide apparatus and methods for performing percutaneous myocardial revascularization that enable autologous angiogenic agents, such as platelets, platelet derived growth factors or cardiomyocytes to be injected into the myocardium adjacent to the PMR channels.
These and other objects of the present invention are accomplished by providing methods for collecting and processing autologous biological materials to form autologous angiogenic agents.
Apparatus and methods also are provided for performing percutaneous myocardial revascularization that includes an injection needle disposed in spaced-apart relation to the channel-forming tool, so that a predetermined amount of the autologous angiogenic agent may be injected into the myocardium adjacent to the PMR channel.
In accordance with the principles of the present invention, blood, cardiomyocytes, or other biological material is first collected from a patient scheduled to undergo PMR. The biological material is then treated to concentrate and activate or express one or more platelet derived growth factors, and is stored in preparation for re-injection into the patient""s myocardium during a PMR procedure.
Apparatus suitable for implementing the methods of the present invention comprises a catheter having an end region that is directable to contact a patient""s endocardium at a plurality of positions. Preferably, the catheter comprises inner and outer catheters each having preformed distal bends, so that the distal end of the inner catheter is directable to a plurality of positions. A cutting head is disposed within a lumen of the inner catheter and coupled to a drive tube that rotates and reciprocates the drive shaft. The drive tube is coupled to a motor that imparts rotational motion to the drive tube. The cutting head and drive tube include a lumen through which severed tissue is aspirated.
One or more stabilizing elements, are disposed on the distal end to retain the inner catheter in position while the cutting head is reciprocated beyond a distal endface of the inner catheter. In accordance with the present invention, the stabilizing elements also serve as injection needles for the re-injecting autologous angiogenic agent into the patient""s myocardium in the vicinity of the channels formed by the cutting head. Methods of using the apparatus to deliver angiogenic agents also are described.